Research On The Expression Of VEGF And VEGI And Their Correlation With Clinicopathological Features Of Colorectal Carcinoma

[Background] It has been well documented that angiogenesis is one of the mostcrucial step facilitating tumour growth. Angiogenesis is tightly regulated by a networkof pro-angiogenic and anti-angiogenic. The tumour itself produce many of the factorsthat drive angiogenesis, such as vascular endothelial growth factor(VEGF), iscommonly related to increased microvessel density (MVD). Therefore, Vascularendothelial growth inhibitor (VEGI) is a novel anti-angiogenic cytokine that belongsto the tumour necrosis factor superfamily, has been identified as a highly effectiveendogenous inhibitor for endothelial growth and angiogenesis and very little is knownabout the significance of VEGI and correlation with cancer.[Objective] To determine the expressions of VEGF and VEGI in colorectalcarcinoma, investigate their correlation with MVD, reveal the basic mechanism ofangiogenesis in tumor malignancy, and demonstrate the correlation betweenexpressions of these molecules and clinicopathological manifestations of colorectalcancer.[Methods] The carcinoma tissues and surgical marginal tissues of colorectal cancerwere harvested from 33 patients which underwent operation. Medical records andpathologic results of all cases were reviewed. The levels of mRNA transcription andprotein expression of VEGF and VEGI were assayed by RT-PCR and Western blotrespectively, as well as MVD were mensurated using immunohistochemical stain withCD34 mAb.[Results] There were significant differences comparing mRNA transcription andprotein expressions of VEGF and VEGI in carcinoma tissues with those in surgicalmarginal tissues. The expressions of VEGF molecule in carcinoma tissues weresignificantly higher than those in surgical marginal tissues, while the expressions ofVEGI molecule in carcinoma tissues were lower than those in surgical marginaltissues. The high correlativity of level of mRNA transcription and level of proteinexpression were detected not only in VEGF but also in VEGI. There were a negativecorrelativity between the expressions of VEGF and VEGI in tumor tissues and apositive one in surgical marginal tissues. The calculation of MVD in carcinomatissues was significantly increasing than that in surgical marginal tissues. Theexpression levels of mRNA and protein of VEGF and VEGI were significantdifferences when tumors infiltrate over serosa, lymph nodes metastasize, andpathologic stage are in Dukes C and D. The over expression of VEGF and the lower expression of VEGI were demonstrated in aforesaid situations respectively. MVD oftumor tissue was higher in group of positive lymphatic node and in stage of Dukes Cand D. There were a positive correlativity between VEGF and MVD and a negativeone between VEGI and MVD in tumor tissues.[Conclusion] Angiogenesis could help to transport oxygen and nutrients to thetumour, which is essential for tumour development. It has been shown that tumourangiogenesis is correlated with tumour malignancy and patient prognosis. Endogenousmolecules VEGF and VEGI played the key roles in angiogenic druation of colorectalcarcinoma and presented opposite effect. Also, the correlation between these twomolecules and histopathologic features of colorectal cancer was proved. VEGI is oneof important negative regulators controlling angiogenesis of colorectal cancer andsuggesting a normal physiological role for the molecule in maintaining a stablevasculature. The redundant of tumor VEGF expression and absence/reduction oftumor VEGI expression suggested that there may have been one of bases of richvascular malignancy due to shifting in the balance between pro-and anti-stimuli andtriggering advantaged environment for angiogenesis. It is demonstration that not onlyVEGF but also VEGI affect the occurrence and development of malignant colorectaltumor.